tbuckley/cabot-search huggingface dataset:
Expansion of the fertility preservation program to all newly diagnosed prepubertal oncology patients at a pediatric hospital.
Authors: Antonia Pryor Leavitt, Karen H. Albritton, Mary Cazzell, Eleanor Stevenson
Journal: Journal of Clinical Oncology (2023)

10064 Background: As the majority of pediatric oncology patients survive their disease, generating a population of over 500,000 survivors in the United States, it is imperative to minimize the lifelong consequences of treatment, which includes temporary or permanent infertility caused by certain cancer treatments. Fertility preservation (FP), the opportunity to preserve one’s ability to have genetically-related children prior to damaging the reproductive system, is a young but rapidly expanding field and recent scientific advances have led to an expansion of options for prepubertal patients. A fertility consultation at diagnosis can provide patients and families with the opportunity to be informed regarding likelihood of gonadal dysfunction and to consider FP. Methods: After our pediatric hospital started to offer tissue cryopreservation, we initiated this evidence-based interventional quality improvement project. Our primary aim was to ensure that all newly diagnosed prepubertal oncology patients who met criteria for FP were correctly identified and offered an educational consultation and preservation. Inpatient admission lists and provider schedules were reviewed daily to identify patients. Treatment plans were discussed with providers to calculate infertility risk. All procedures were to be completed at the time of another procedure to increase likelihood of insurance coverage and minimize delays. Results: Between 07/15/22 and 11/30/22, 54 newly diagnosed prepubertal patients’ treatment plans were evaluated to determine treatment-related infertility risk using the Oncofertility Consortium Pediatric Initiative Network’s Risk Assessment tool. 15 patients were at a high level of significantly increased risk and were therefore eligible for consultation. 7 patients and their families received an educational consultation and 6 elected to undergo FP (3 TTCs; 3 OTCs). FP procedures did not cause a delay in starting treatment for any of these patients. 8 patients did not receive consultations. Reasons included the provider electing to proceed with treatment without consultation (4), the patient’s comorbidities (1), the inability to bundle FP with another procedure (1), and the family decision to decline consultation (1). Conclusions: Of the patients at high risk of infertility, only 46% received consultation with lack of referral prior to initiating treatment as the primary reason. Of the patients offered preservation methods, 86% elected to preserve their fertility, illustrating patient and family interest. Providers must acknowledge changes in practice and be informed on the impact that high-risk treatment protocols can have on fertility. An FP program with established policies processes can increase the likelihood that prepubertal patients at high risk for infertility are correctly identified, educated, and offered preservation.
Treatment patterns and clinical outcomes of newly diagnosed locally advanced head and neck squamous cell carcinoma (LA HNSCC): A retrospective cohort analysis of national real-world data in England.
Authors: Chris M. Black, Anthony Kong, Gavin Chiu, John Bolodeoku, Olivia Massey, Amisha Patel, Alexander Ford, Tim Holbrook
Journal: Journal of Clinical Oncology (2023)

e18075 Background: LA HNSCC (stage III-IVb) is a potentially curable disease. However, many patients experience recurrence and metastasis, resulting in poorer prognoses. The multimodal approach to treating LA HNSCC makes the evaluation of treatment regimens difficult. This study aimed to describe the real-world treatment patterns, clinical outcomes and HCRU of LA HNSCC patients in England. Methods: This retrospective cohort study involved the use of data from the National Cancer Registration and Analysis Service databases (Cancer Registry, Systemic Anti-Cancer Therapy, Hospital Episode Statistics [HES], National Radiotherapy Dataset and Diagnostic Imaging Dataset). Adults with a first record of primary LA HNSCC between 01/01/2015 and 31/12/2018 were indexed. Treatment pathways and clinical outcomes were investigated over a maximum of 5-years follow-up period extending to 31 st December 2020. Results: 12,790 patients were included within the cohort. 52.1% (n = 6,665) received chemotherapy at some point during follow-up as part of their combination treatment with surgery and/or radiotherapy. Within the chemotherapy receiving cohort, 21.2% (n = 1,413) received induction chemotherapy prior to surgery or radiotherapy, 92.2% (n = 6,145) received concurrent chemo-radiotherapy and 11.8% (n = 787) received chemotherapy following surgery or radiotherapy, suggesting palliative treatment. The majority of chemotherapy regimens used were platinum-based. Of those receiving surgery (n = 5,292), the most common type of surgery was transoral surgery, occurring in 51.3% of the resectable patients. 40.2% of the overall cohort received salvage surgery during follow-up. 50.1% and 12.4% of patients experienced locoregional or distant metastatic progression, respectively and 39.2% of the cohort died. The 5-year overall survival (OS) was ~59% and ~55% for resected and unresected patients respectively. For event free survival (EFS), the 5-year median survival time post event free state index for the overall cohort was 12.32 months. Median survival time for the different tumour sites ranged from 19.4 and 2.6 months, with the nasopharynx and ‘other’ site group representing these range ends respectively. The highest HCRU/costs were incurred within the first 3 months following diagnosis; mean number of HNSCC-related inpatient stays were 2.93 (SD = 4.05), costing a total of £57,781,497 (per patient: £4,855.18 [£5872.05], mean[SD]). Conclusions: This is the first real world study using the UK NCRAS datasets to assess the treatment pathway and outcomes of the LA HNSCC population in England. Survival outcomes varied across site of primary tumour and patients diagnosed at stage 4 experienced poorer outcomes, highlighting the need for improved treatment plans and clinical outcomes for this patient population.
Phase 2 study of bavituximab (bavi), a first-in-class antibody targeting phosphatidylserine (PS), plus pembrolizumab (P) in advanced gastric or gastroesophageal junction (GEJ) cancer.
Authors: Jeeyun Lee, Ardaman Shergill, Haeseong Park, Keun-Wook Lee, Hendrik-Tobias Arkenau, Yoon-Koo Kang, Olugbenga Olanrele Olowokure, Jong Gwang Kim, Sung Yong Oh, Do-Youn Oh, Dan Costin, Andrew William Pippas, Jen-Shi Chen, Marya F. Chaney, Andrew Koustenis, Hagop Youssoufian, Lukas Makris, Kerry Culm, Colleen M. Mockbee, Ian Chau
Journal: Journal of Clinical Oncology (2023)

e16023 Background: Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of PS through interaction with TIM/TAM receptor family members in the tumor microenvironment (TME), was evaluated in combination with P in patients with advanced gastric and GEJ cancer. Methods: ONCG100 was a phase 2, multicenter, open-label, two-cohort global study designed to assess the safety, tolerability, and antitumor activity of bavi (3 mg/kg, QW) plus P (200 mg, Q3W) in advanced gastric or GEJ cancer patients who progressed on ≥1 prior standard therapy (NCT04099641). Patients were checkpoint inhibitor (CPI) naive (Grp 1) or CPI relapsed (Grp 2); known MSI-H patients were excluded. RNA expression was analyzed in pre-treatment tumor tissue using the Xerna TME Panel, an RNA-based diagnostic, to prospectively test hypothesis that tumors with high immune or immune-suppressed TME subtypes (B+) are more likely to respond to bavi plus P than high angiogenic/immune-desert TME subtypes (B-). Results: A total of 80 patients enrolled (Grp 1 n=61, Grp 2 = 19). The most frequently reported Grade ≥ 3 treatment emergent adverse events (occurring in ≥10% of patients overall) were anaemia and gastric cancer progression (n= 10/AE). Key efficacy parameters for Grp 1 patients (2L 57.4%) are summarized in Table 1. In Grp 2, the ORR was 5.3% (95% CI: 0.1, 26.0), whereby 0 patients achieved a complete response and only 1 (5.3%) patient achieved a partial response as the best overall response (BOR). In the remaining patients, BOR was stable disease in 9 (47.4%) patients, progressive disease in 8 (42.1%) patients, and not evaluable in 1 (5.3%) patient. Conclusions: The combination of Bavi and P was well tolerated; observed AEs were consistent with known profiles for each agent. Higher ORRs were observed in CPI-naïve patients with B+ status and baseline NLR&lt;4, and of note, in patients with PD-L1 CPS &lt;1. Future studies may be planned to confirm the activity of Bavi in combination with P with patient selection based on a particular genetic signature. Clinical trial information: NCT04099641 . [Table: see text]
Efficacy and safety of radiotherapy combined with regorafenib for advanced hepatocellular carcinoma: A real-world study from a single center.
Authors: Lingxia Xin, Liming Wang, Yirui Zhai, Shulian Wang, Yuan Tang, Yueping Liu, Yongwen Song, Hui Fang, Ning Li, Shunan Qi, Ningning Lu, Ye-Xiong Li, Bo Chen
Journal: Journal of Clinical Oncology (2023)

e16142 Background: This study aimed to assess the efficacy and safety of radiotherapy (RT) combined with regorafenib as a second or further-line treatment for advanced hepatocellular carcinoma (HCC). Methods: Patients diagnosed with advanced HCC who had received RT combined with concurrent or sequential regorafenib treatment or regorafenib plus anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICIs) in our hospital from April 2018 to August 2022 were reviewed. Progression-free survival (PFS) was the primary endpoint. Overall survival (OS), objective response rate (ORR), disease control rate (DCR) and toxicity were the secondary endpoints. Results: Fifty-four patients were included with a median age of 56 (38-73). Forty-six patients (85.2%) were in Barcelona Clinic Liver Cancer (BCLC) stage C. Thirty-seven patients (68.5%) had portal vein tumor thrombosis and 15 (27.8%) had extrahepatic metastasis. All patients received intensity modulated radiation therapy, while 26 patients were concurrently treated with regorafenib and 28 patients were sequentially treated with regorafenib. The median dose of radiotherapy was 57.2Gy (30-69.8Gy). Anti-PD-1/anti-PD-L1 agents were applied to 31 patients at the use of regorafenib. The median PFS was 11.3 months. The 3-year PFS and OS were 23.8% and 51.9%, respectively. Treatment response after RT was shown. For tumor in in-field of RT, ORR was 75.9% and 92.6% according to RECIST and mRECIST criteria, respectively. No progression was found in in-field of RT. Out-field recurrence in liver and distance metastasis was the main failure pattern. For all lesions, the ORR was 40.7% and DCR was 55.6%, respectively. There was no significant difference of PFS and OS between patients with and without ICIs ( p &gt; 0.05). Univariate analysis showed that alpha-fetoprotein tumor marker level ≥ 1000 ng/ml ( p = 0.049), Albumin-Bilirubin grade ≥ 2 ( p = 0.012) and multiple intrahepatic tumors ( p = 0.031) were the risk factors of lower PFS. Patients were well tolerated to the treatments. The most common grade 3 toxicities were hand-foot syndrome (11.1%), fatigue (3.7%) and hypertension (1.9%). Classical or non-classical radiation-induced liver disease was not noted. Conclusions: Radiotherapy concurrently or sequentially with regorafinib treatment is an effective, well tolerated, and promising regimen in advanced HCC patients. [Table: see text]
Liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): 12- and 18-month survival rates from the phase 3 NAPOLI 3 trial.
Authors: Eileen Mary O'Reilly, Davide Melisi, Teresa Macarulla, Roberto A. Pazo Cid, Sreenivasa R Chandana, Christelle De La Fouchardiere, Andrew Peter Dean, Igor Kiss, Woo Jin Lee, Thorsten Oliver Goetze, Eric Van Cutsem, Scott Paulson, Tanios S. Bekaii-Saab, Shubham Pant, Richard Hubner, Zhimin Xiao, Huanyu Chen, Fawzi Benzaghou, Zev A. Wainberg
Journal: Journal of Clinical Oncology (2023)

4006 Background: Liposomal irinotecan + 5-fluorouracil/leucovorin (5-FU/LV) is approved in the USA and Europe for mPDAC following progression with gemcitabine-based therapy. A phase 1/2 study (NCT02551991) demonstrated promising anti-tumor activity in patients with mPDAC who received first-line liposomal irinotecan 50 mg/m 2 + 5-FU 2400 mg/m 2 + LV 400 mg/m 2 + oxaliplatin 60 mg/m 2 (NALIRIFOX). Here, we present results from NAPOLI 3 (NCT04083235), a randomized, open-label, phase 3 study investigating the efficacy and safety of NALIRIFOX compared with nab-paclitaxel 125 mg/m 2 + gemcitabine 1000 mg/m 2 (Gem+NabP) as first-line therapy in patients with mPDAC. Methods: Eligible patients with histopathologically/cytologically confirmed untreated mPDAC were randomized (1:1; stratified by Eastern Cooperative Oncology Group [ECOG] performance status, geographic region and presence/absence of liver metastases) to receive NALIRIFOX on days 1 and 15 of a 28-day cycle or Gem+NabP on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), overall response rate (ORR) and safety. OS was evaluated when at least 543 events were observed using a stratified log-rank test with an overall one-sided significance level of 0.025. Results: Overall, 770 patients (NALIRIFOX, n = 383; Gem+NabP, n = 387) were included. Baseline characteristics were balanced between arms. At a median follow-up of 16.1 months, 544 events had occurred. Median OS was 11.1 months in the NALIRIFOX group versus 9.2 months in the Gem+NabP group; median PFS was 7.4 months versus 5.6 months. Median (95% CI) duration of response was 7.3 (5.8–7.6) and 5.0 (3.8–5.6) months in patients who received NALIRIFOX and Gem+NabP, respectively. Grade 3/4 treatment-emergent adverse events occurring in at least 10% of patients receiving NALIRIFOX versus Gem+NabP included diarrhea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), hypokalemia (15.1% vs 4.0%), anemia (10.5% vs 17.4%) and neutropenia (14.1% vs 24.5%). Conclusions: First-line NALIRIFOX demonstrated clinically meaningful and statistically significant improvement in OS and PFS compared with Gem+NabP in patients with mPDAC. The NALIRIFOX safety profile was consistent with the profiles of the regimen components and generally manageable. Clinical trial information: NCT04083235 . [Table: see text]
An in-house testing for detection of homologous recombination repair deficiency (HRD) in patients with solid tumors.
Authors: Shuguang Tan, Weifeng Guo, Bin Cai, Tianhao Mu, Ming Liu, Zhouyang Wang, Yanqing Zhou, Yan Yin
Journal: Journal of Clinical Oncology (2023)

e15025 Background: HRD is associated with sensitivity towards PARP inhibitors (PARPi) in various cancer types, such as ovarian cancer, breast cancer, pancreatic cancer, and prostate cancer, and its determination is used as a biomarker for therapy decision making. HRD leads to the larger genome alterations, called “genomic scars“, which comprise loss of heterozygosity (LOH), telomeric allelic imbalance (TAI) and large scale state transitions(LST). The detection of SNPs is capable of measuring chromosomal abnormalities including genomic scars as mentioned above. Methods: Using a panel targeting more than 50,000 SNPs that evenly spaced across the entire human genome and the next generation sequencing technique, we developed an in-house testing for HRD detection, namely HRD score, which was computed by combining the measurements of large genomic defects including LOH, TAI, and LST. Then, we detected 44 ovarian cancer patients without BRCA1/2 mutations and 14 ovarian cancer patients harboring BRCA1/2 mutations to explore the application possibility of HRD score 42 as the threshold for HRD patients. Furthermore, we studied the HRD score distribution of 494 solid tumor patients. Results: For the 44 ovarian cancer patients without BRCA mutation, 50% (22/44) of them had the HRD score greater than 42. For the 14 ovarian cancer patients harboring BRCA1/2 mutations, 100%(14/14) of them had the HRD score greater than 42. For the 494 solid tumor patients, 38.66% (191/494) of them had the HRD score greater than 42. Conclusions: For this in-house HRD testing, the percentage of ovarian cancer patients without BRCA mutation who had HRD score greater than 42 was consistent with former report. Besides, the HRD score of all the 14 ovarian cancer patients harboring BRCA1/2 mutations were greater than 42, which was consistent with the facts. Therefore, it seems applicable to define the patients with HRD score greater than 42 as HRD positive. In addition, there is a wide range of demands for comprehensive implementation of HRD testing for other tumor entities.
Prediction of brain metastases progression and overall survival in patients with metastatic non-small cell lung cancer treated by immune checkpoint inhibitors using a radiomic model.
Authors: Clemence Henon, Lizza Hendriks, Alexandre Carré, Laura Mezquita, Sylvain Reuzé, Samy Ammari, Mihaela Aldea, Charlotte Robert, Cecile Le Pechoux, Clarisse Audigier-Valette, Julien Mazieres, Corentin Lefebvre, Audrey Rabeau, Boris Duchemann, Angela Botticella, David Planchard, Eric Deutsch, Benjamin Besse, Roger Sun
Journal: Journal of Clinical Oncology (2023)

e21169 Background: Brain metastases (BMs) incidence is high in patients with metastatic non-small cell lung cancer (NSCLC). Immune Checkpoints Inhibitors (ICIs) are now standard of care for metastatic NSCLC in the first-line or beyond settings. However, less than half of patients will have a tumor response, and the determinants of BMs response to ICIs remain unknown. This study aims to evaluate the value of radiomics to predict control/progression of BMs at a lesion level, and outcomes at a patient level in the BM+ NSCLC population treated by ICIs. Methods: We conducted a retrospective multicenter (5 European centers) study including consecutive patients with NSCLC BMs and available baseline MRI before ICIs (evaluation cohort) or chemotherapy (control cohort) with a 2:1 ratio, between 2011 and 2021. After modified RANO (Response Assessment in Neuro-Oncology) assessment of individual BMs, we developed a radiomic model to predict BMs control/progression to ICIs at the first brain follow-up imaging. The ICIs cohort was split into two datasets used for (i) model training with 5-fold cross-validation and (ii) model testing. The Chemotherapy cohort was used to ensure the specificity of our model to ICIs-treated patients. Results: Ninety-four and 49 patients were included in the ICIs and Chemotherapy cohorts respectively, of which 56 (59.6%, N = 227 BMs) and 39 (79.6%, N = 192 BMs) patients had available brain follow-up imaging. The ICIs cohort was specifically enriched in radiomic features which were significantly associated to BMs progression. Our final model, based on extreme gradient boosting (xgboost) on BMs &gt; 10mm from the training set (N = 39 BMs), could predict individual BMs progression to ICIs with an area under curve (AUC) of 0.77 (p-value = 0.029, 95% CI [0.56-0.98]) in the test set (N = 20 BMs). We further generated a radiomic score to stratify BM+ NSCLC ICIs-treated patients between High-Risk or Low-Risk groups according to the predicted individual BMs progression. High-risk patients were associated with worse overall survival (OS) (median OS of 6.3 months, 95% CI [3.02-10.49]) compared to Low-risk patients (median OS of 11.87 months, 95% CI [7.02-21.90], p = 0.042). The prognostic value of the radiomic score on OS was validated in a multivariate analysis in the ICIs cohort (Table). Conclusions: To our knowledge, this is the first study to explore the value of radiomics in the prediction of BMs response to immunotherapy. Prospective evaluation will confirm the generalizability of our model in clinical practice.[Table: see text]
The analysis of BRAF fusions characteristics in Chinese solid tumor patients.
Authors: Fang Ma, Yaping Zhao, Chenxi Wang, Tiantian Han, Ran Ding, Wanglong Deng, Fanfeng Bu
Journal: Journal of Clinical Oncology (2023)

e15073 Background: BRAF encodes a RAF kinase, which signal downstream of RAS and activate the MAPK pathway, and has emerged as a major oncogenic driver and a potential therapy target. BRAF V600E base substitution is an approved target for the BRAF inhibitors in solid tumors. BRAF gene fusions represent a different mechanism of BRAF activation. BRAF fusions have shown responses to MEK inhibitors and non-specific RAF inhibitors (eg, sorafenib) in Melanoma (NCCN). We sought to analysis of BRAF fusions characteristics in Chinese solid tumor patients to explore the possibility of therapeutic intervention in solid tumors. Methods: We comprehensively characterized BRAF fusions from next-generation sequencing (NGS) data from May 2019 to January 2023 in 80083 various solid tumors. Considering the characteristics of the receptor tyrosine kinase, we focused on the BRAF fusions which contain the kinase domain. Results: A total of 164 unique cases (70.1% (115/164) glioma and 29.9% (49/164) non-glioma with BRAF fusions) were identified. The non-glioma cohort consisted up mainly lung tumors (49%, 24/49), colorectal tumors (18.4%, 9/49), pancreatic tumors (10.2%,5/49), melanoma (9.2%, 4/49) and biliary tumors (4.1%, 2/49). In the glioma cohort, the median age of the 115 patients was 12 with a range of 0–66; 43 (37.4%) of the patients were female and 72 (62.6%) were male. On the other hand, the median age was 64 with a range of 33–82; 23 (46.9%) of the patients were female and 26 (53.10%) were male in the non-glioma cohort. In the glioma cohort, 82.4% of the partners were KIAA1549. However, the most common fusion partners were AGK (14.04%), TRIM24(14.0%), SND1(12.28%), TPK1(8.77%) in the non-glioma cohort. These BRAF fusions comprised 49 unique 5′ fusion partners, of which 51% (25) were known and 49.0% (24) were novel. 14 novel partners were TMEM176B, HMBOX1, SEMA3E, LOC441204, PDE4D, DENND2A, STIM1, TNS3, PRRC2B, BCR, MET, COL4A3BP, TPM4, ZBTB16 and 10 novel partners were intergenic region. 130 patients with BRAF fusions could be evaluated for concurrent mutations. Of interest is that no KRAS and BRAF V600E mutations were identified in the 130 cases. Conclusions: BRAF fusions were detected in 0.2% (164/80083) of Chinese solid tumor patients. 70.1% of BRAF fusion positive cases were diagnosed with glioma and 29.9% were diagnosed with non-glioma. 14 novel BRAF fusion partners were discovered. BRAF fusion is an important driver genomic alteration and occur in a mutually exclusive pattern with other activating mutations in the MAP kinase signaling pathway. BRAF fusion targeted therapies should be further explored in solid tumors.